JAMA current issue

Context  Hemoglobin-based blood substitutes (HBBSs) are infusible oxygen-carrying liquids that have long shelf lives, have no need for refrigeration or cross-matching, and are ideal for treating hemorrhagic shock in remote settings. Some trials of HBBSs during the last decade have reported increased risks without clinical benefit.

Objective  To assess the safety of HBBSs in surgical, stroke, and trauma patients.

Data Sources  PubMed, EMBASE, and Cochrane Library searches for articles using hemoglobin and blood substitutes from 1980 through March 25, 2008; reviews of Food and Drug Administration (FDA) advisory committee meeting materials; and Internet searches for company press releases.

Study Selection  Randomized controlled trials including patients aged 19 years and older receiving HBBSs therapeutically. The database searches yielded 70 trials of which 13 met these criteria; in addition, data from 2 other trials were reported in 2 press releases, and additional data were included in 1 relevant FDA review.

Data Extraction  Data on death and myocardial infarction (MI) as outcome variables.

Results  Sixteen trials involving 5 different products and 3711 patients in varied patient populations were identified. A test for heterogeneity of the results of these trials was not significant for either mortality or MI (for both, I² = 0%, P ≥ .60), and data were combined using a fixed-effects model. Overall, there was a statistically significant increase in the risk of death (164 deaths in the HBBS-treated groups and 123 deaths in the control groups; relative risk [RR], 1.30; 95% confidence interval [CI], 1.05-1.61) and risk of MI (59 MIs in the HBBS-treated groups and 16 MIs in the control groups; RR, 2.71; 95% CI, 1.67-4.40) with these HBBSs. Subgroup analysis of these trials indicated the increased risk was not restricted to a particular HBBS or clinical indication.

Conclusion  Based on the available data, use of HBBSs is associated with a significantly increased risk of death and MI.

Published online April 28, 2008 (doi:10.1001/jama.299.19.jrv80007).

Context  Screening ultrasound may depict small, node-negative breast cancers not seen on mammography.

Objective  To compare the diagnostic yield, defined as the proportion of women with positive screen test results and positive reference standard, and performance of screening with ultrasound plus mammography vs mammography alone in women at elevated risk of breast cancer.

Design, Setting, and Participants  From April 2004 to February 2006, 2809 women, with at least heterogeneously dense breast tissue in at least 1 quadrant, were recruited from 21 sites to undergo mammographic and physician-performed ultrasonographic examinations in randomized order by a radiologist masked to the other examination results. Reference standard was defined as a combination of pathology and 12-month follow-up and was available for 2637 (96.8%) of the 2725 eligible participants.

Main Outcome Measures  Diagnostic yield, sensitivity, specificity, and diagnostic accuracy (assessed by the area under the receiver operating characteristic curve) of combined mammography plus ultrasound vs mammography alone and the positive predictive value of biopsy recommendations for mammography plus ultrasound vs mammography alone.

Results  Forty participants (41 breasts) were diagnosed with cancer: 8 suspicious on both ultrasound and mammography, 12 on ultrasound alone, 12 on mammography alone, and 8 participants (9 breasts) on neither. The diagnostic yield for mammography was 7.6 per 1000 women screened (20 of 2637) and increased to 11.8 per 1000 (31 of 2637) for combined mammography plus ultrasound; the supplemental yield was 4.2 per 1000 women screened (95% confidence interval [CI], 1.1-7.2 per 1000; P = .003 that supplemental yield is 0). The diagnostic accuracy for mammography was 0.78 (95% CI, 0.67-0.87) and increased to 0.91 (95% CI, 0.84-0.96) for mammography plus ultrasound (P = .003 that difference is 0). Of 12 supplemental cancers detected by ultrasound alone, 11 (92%) were invasive with a median size of 10 mm (range, 5-40 mm; mean [SE], 12.6 [3.0] mm) and 8 of the 9 lesions (89%) reported had negative nodes. The positive predictive value of biopsy recommendation after full diagnostic workup was 19 of 84 for mammography (22.6%; 95% CI, 14.2%-33%), 21 of 235 for ultrasound (8.9%, 95% CI, 5.6%-13.3%), and 31 of 276 for combined mammography plus ultrasound (11.2%; 95% CI. 7.8%-15.6%).

Conclusions  Adding a single screening ultrasound to mammography will yield an additional 1.1 to 7.2 cancers per 1000 high-risk women, but it will also substantially increase the number of false positives.

Trial Registration  clinicaltrials.gov Identifier: NCT00072501

Context  The arteriovenous fistula is the preferred type of vascular access for hemodialysis because of lower thrombosis and infection rates and lower health care expenditures compared with synthetic grafts or central venous catheters. Early failure of fistulas due to thrombosis or inadequate maturation is a barrier to increasing the prevalence of fistulas among patients treated with hemodialysis. Small, inconclusive trials have suggested that antiplatelet agents may reduce thrombosis of new fistulas.

Objective  To determine whether clopidogrel reduces early failure of hemodialysis fistulas.

Design, Setting, and Participants  Randomized, double-blind, placebo-controlled trial conducted at 9 US centers composed of academic and community nephrology practices in 2003-2007. Eight hundred seventy-seven participants with end-stage renal disease or advanced chronic kidney disease were followed up until 150 to 180 days after fistula creation or 30 days after initiation of dialysis, whichever occurred later.

Intervention  Participants were randomly assigned to receive clopidogrel (300-mg loading dose followed by daily dose of 75 mg; n = 441) or placebo (n = 436) for 6 weeks starting within 1 day after fistula creation.

Main Outcome Measures  The primary outcome was fistula thrombosis, determined by physical examination at 6 weeks. The secondary outcome was failure of the fistula to become suitable for dialysis. Suitability was defined as use of the fistula at a dialysis machine blood pump rate of 300 mL/min or more during 8 of 12 dialysis sessions.

Results  Enrollment was stopped after 877 participants were randomized based on a stopping rule for intervention efficacy. Fistula thrombosis occurred in 53 (12.2%) participants assigned to clopidogrel compared with 84 (19.5%) participants assigned to placebo (relative risk, 0.63; 95% confidence interval, 0.46-0.97; P = .018). Failure to attain suitability for dialysis did not differ between the clopidogrel and placebo groups (61.8% vs 59.5%, respectively; relative risk, 1.05; 95% confidence interval, 0.94-1.17; P = .40).

Conclusion  Clopidogrel reduces the frequency of early thrombosis of new arteriovenous fistulas but does not increase the proportion of fistulas that become suitable for dialysis.

Trial Registration  clinicaltrials.gov Identifier: NCT00067119

Context  Health risks of fine particulate matter of 2.5 µm or less in aerodynamic diameter (PM_2.5) have been studied extensively over the last decade. Evidence concerning the health risks of the coarse fraction of greater than 2.5 µm and 10 µm or less in aerodynamic diameter (PM_10-2.5) is limited.

Objective  To estimate risk of hospital admissions for cardiovascular and respiratory diseases associated with PM_10-2.5 exposure, controlling for PM_2.5.

Design, Setting, and Participants  Using a database assembled for 108 US counties with daily cardiovascular and respiratory disease admission rates, temperature and dew-point temperature, and PM_10-2.5 and PM_2.5 concentrations were calculated with monitoring data as an exposure surrogate from January 1, 1999, through December 31, 2005. Admission rates were constructed from the Medicare National Claims History Files, for a study population of approximately 12 million Medicare enrollees living on average 9 miles (14.4 km) from collocated pairs of PM₁₀ and PM_2.5 monitors.

Main Outcome Measures  Daily counts of county-wide emergency hospital admissions for primary diagnoses of cardiovascular or respiratory disease.

Results  There were 3.7 million cardiovascular disease and 1.4 million respiratory disease admissions. A 10-µg/m³ increase in PM_10-2.5 was associated with a 0.36% (95% posterior interval [PI], 0.05% to 0.68%) increase in cardiovascular disease admissions on the same day. However, when adjusted for PM_2.5, the association was no longer statistically significant (0.25%; 95% PI, –0.11% to 0.60%). A 10-µg/m³ increase in PM_10-2.5 was associated with a nonstatistically significant unadjusted 0.33% (95% PI, –0.21% to 0.86%) increase in respiratory disease admissions and with a 0.26% (95% PI, –0.32% to 0.84%) increase in respiratory disease admissions when adjusted for PM_2.5. The unadjusted associations of PM_2.5 with cardiovascular and respiratory disease admissions were 0.71% (95% PI, 0.45%-0.96%) for same-day exposure and 0.44% (95% PI, 0.06% to 0.82%) for exposure 2 days before hospital admission.

Conclusion  After adjustment for PM_2.5, there were no statistically significant associations between coarse particulates and hospital admissions for cardiovascular and respiratory diseases.

Context  Safety-net hospitals (ie, those that predominantly treat poor and underserved patients) often have lower quality of care than non–safety-net hospitals. While public reporting and pay for performance have the potential to improve quality of care at poorly performing hospitals, safety-net hospitals may be unable to invest in quality improvement. As such, some have expressed concern that these incentives have the potential to worsen existing disparities among hospitals.

Objective  To examine trends in disparities of quality of care between hospitals with high and low percentages of Medicaid patients.

Design and Setting  Longitudinal study of the relationship between hospital performance and percentage Medicaid coverage from 2004 to 2006, using publicly available data on hospital performance. A simulation model was used to estimate payments at hospitals with high and low percentages of Medicaid patients.

Main Outcome Measures  Changes in hospital performance between 2004 and 2006, estimating whether disparities in hospital quality between hospitals with high and low percentages of Medicaid patients have changed.

Results  Of the 4464 participating hospitals, 3665 (82%) were included in the final analysis. Hospitals with high percentages of Medicaid patients had worse performance in 2004 and had significantly smaller improvement over time than those with low percentages of Medicaid patients. Hospitals with low percentages of Medicaid patients improved composite acute myocardial infarction performance by 3.8 percentage points vs 2.3 percentage points for those with high percentages, an absolute difference of 1.5 (P = .03). This resulted in a relative difference in performance gains of 39%. Larger performance gains at hospitals with low percentages of Medicaid patients were also seen for heart failure (difference of 1.4 percentage points, P = 0.04) and pneumonia (difference of 1.3 percentage points, P <.001). Over time, hospitals with high percentages of Medicaid patients had a lower probability of achieving high-performance status. In a simulation model, these hospitals were more likely to incur financial penalties due to low performance and were less likely to receive bonuses.

Conclusions  Safety-net hospitals tended to have smaller gains in quality performance measures over 3 years and were less likely to be high-performing over time than non–safety-net hospitals. An incentive system based on these measures has the potential to increase disparities among hospitals.

A 19-year-old woman living with relatives in the United States who was admitted for elective cranial surgery for complications related to a congenital disorder developed an acute intracranial hemorrhage 10 days after surgery. The patient was declared dead following repeat negative apnea tests. The patient's father requested that the treating team administer an unverified traditional medicinal substance to the patient. Because of the unusual nature of this request, the treating team called an ethics consultation. The present article reviews this case and discusses other cases that share key features to determine whether and when it is appropriate to accommodate requests for interventions on patients who have been declared dead.